2-Fluoropyridine → HCID 10199257, compound

HRID 1937623Notes

Reaction equation

HRID 1937623 reaction equation
[CH3:1][C:2]1([CH3:14])[CH2:10][C:9]2[NH:8][CH:7]=[C:6]([CH2:11][CH3:12])[C:5]=2[C:4](=[O:13])[CH2:3]1.[H-].[Na+].F[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=1>CN(C=O)C>[CH3:14][C:2]1([CH3:1])[CH2:10][C:9]2[N:8]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)[CH:7]=[C:6]([CH2:11][CH3:12])[C:5]=2[C:4](=[O:13])[CH2:3]1

Participants

5

Reactant 3

HCID 97462-FluoropyridineHCID 24758Sodium hydrideHCID 22461260HCID 22461260, compound

Product 1

HCID 10199257HCID 10199257, compoundYield 26%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6,6-dimethyl 3-ethyl-4,5,6,7-tetrahydro-1H-indol-4-one (50 mg, 0.26 mmol) in DMF (4 mL) at 0° C., was added NaH (11 mg of a 60% dispersion in mineral oil, 0.29 mmol). The cooling bath was removed and the mixture stirred at room temperature for 20 min. After this time 2-fluoropyridine (26 μl, 0.29 mmol) was added and the residue heated at 90° C. for 6 h. The solvent was evaporated and the residue partitioned between EtOAc (20 mL) and water (20 mL). The organic layer was separated, dried (Na2SO4) and evaporated. The residue was chromatographed an silica gel, eluting with hexane:EtOAc (2:1), to give the title pyrrole (18 mg, 26%) as a colourless solid. mp 125-127° C. 1H NMR (360 MHz, CDCl3) δ 1.10 (6H,s), 1.23 (3H,t,J=7.4 Hz), 2.38 (2H,s), 2.83 (2H,d of q, J=7.4 and 1.0 Hz), 2.92 (2H,s), 6.88 (1H,s), 7.25-7.27 (1H,m), 7.30 (1H,d,J=8.0 Hz), 7.82 (1H,d of t, J=7.7 and 1.9 Hz), 8.51-8.57 (1H,m). MS (ES+) 269 (M+1).

Workup

  1. customThe cooling bath was removed
  2. temperaturethe residue heated at 90° C. for 6 h
  3. customThe solvent was evaporated
  4. customthe residue partitioned between EtOAc (20 mL) and water (20 mL)
  5. customThe organic layer was separated
  6. dry with materialdried (Na2SO4)
  7. customevaporated
  8. customThe residue was chromatographed an silica gel
  9. washeluting with hexane:EtOAc (2:1)

Sources & evidence

ORD record
ord-99aec22924854113b22c7f1848e2d93a
Source dataset
uspto-grants-2002_05
Patent number
US06395766B1

Reaction notes

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